6-30912980-G-A

Variant names:

• chr6-30912980-G-A
• rs1264307
• NM_001517.5:c.1090-130G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001517.5(GTF2H4):​c.1090-130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 797,246 control chromosomes in the GnomAD database, including 43,954 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6815 hom., cov: 31)
  • Exomes 𝑓: 0.33 (37139 hom.)
• Consequence: GTF2H4 NM_001517.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 23 publications found

Genes affected

GTF2H4 (HGNC:4658): (general transcription factor IIH subunit 4) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in nuclear speck. Part of core TFIIH complex portion of holo TFIIH complex and transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288473 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2H4	NM_001517.5	c.1090-130G>A		intron_variant	Intron 11 of 13	ENST00000259895.9	NP_001508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2H4	ENST00000259895.9	c.1090-130G>A		intron_variant	Intron 11 of 13	1	NM_001517.5	ENSP00000259895.4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42504 AN: 151940 Hom.: 6818 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.330 AC: 213098 AN: 645188 Hom.: 37139 AF XY: 0.329 AC XY: 109936 AN XY: 333734

African (AFR) AF: 0.117 AC: 1967 AN: 16762

American (AMR) AF: 0.218 AC: 5257 AN: 24088

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 5914 AN: 15934

East Asian (EAS) AF: 0.232 AC: 7558 AN: 32558

South Asian (SAS) AF: 0.272 AC: 14281 AN: 52580

European-Finnish (FIN) AF: 0.382 AC: 16182 AN: 42380

Middle Eastern (MID) AF: 0.319 AC: 1260 AN: 3944

European-Non Finnish (NFE) AF: 0.355 AC: 150703 AN: 424594

Other (OTH) AF: 0.308 AC: 9976 AN: 32348

GnomAD4 genome AF: 0.280 AC: 42514 AN: 152058 Hom.: 6815 Cov.: 31 AF XY: 0.281 AC XY: 20863 AN XY: 74314

African (AFR) AF: 0.125 AC: 5176 AN: 41512

American (AMR) AF: 0.242 AC: 3700 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1391 AN: 3468

East Asian (EAS) AF: 0.253 AC: 1307 AN: 5168

South Asian (SAS) AF: 0.263 AC: 1263 AN: 4810

European-Finnish (FIN) AF: 0.392 AC: 4141 AN: 10558

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24568 AN: 67936

Other (OTH) AF: 0.279 AC: 589 AN: 2112

Alfa AF: 0.327 Hom.: 21534

Bravo AF: 0.263

Asia WGS AF: 0.207 AC: 725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.77
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1264307; hg19: chr6-30880757;